Bone densitometer providing assessment of absolute fracture risk

ABSTRACT

A bone densitometer accepts inputs of non-bone density patient information to provide a measure of absolute fracture risk to provide a more accurate and personal assessment of osteoporosis. A simple graphical output compares this risk to standard populations.

BACKGROUND OF INVENTION

[0001] The present invention relates to diagnostic medical equipment andin particular to a bone densitometer providing an output indicatingabsolute risk of bone fracture.

[0002] Bone densitometers provide a measurement of bone mineral density(BMD) typically using x-ray or ultrasound measurement. Normally this BMDvalue is an areal density measurement, e.g., g/cm², however, volumedensity measurements, e.g. g/cm³, may also be provided using, forexample, tomographic reconstruction.

[0003] BMD measurements may be made at various locations on the body butare most frequently conducted on the bones of the lumbar vertebra, thefemoral neck, or the os calcis of the heel.

[0004] X-ray and ultrasound densitometers are described in U.S. Pat.Nos. 6,438,201, 6,364,837, 6,277,076, 6,246,747, 6,215,846, 6,160,866,6,081,582, 6,038,281, 6,027,449, RE36162, 5,841,833, 5,840,029, and5,748,704, among others, assigned to the assignee of the presentinvention and hereby incorporated by reference.

[0005] A raw BMD value has limited meaning to a physician or patient andso current densitometers normally provide a comparison of the measuredBMD value to an established reference. One such reference is a T-score,which compares the patient's BMD value to the expected value of BMD fora young adult of the same gender. The T-score provides a qualitativeindication of risk of fracture in that the greater the negative value ofthe T-score, the greater the risk of fracture.

[0006] Alternatively, a logistic regression analysis may be used todetermine a quantitative relationship between BMD and relative fracturerisk based on a recognized mathematical relationship between decline inBMD and increased risk of fracture. This relationship has beendetermined prospectively in empirical studies of elderly populations andconsiders the difference between the patient and someone of the same ageand gender.

[0007] Desirably, bone densitometry equipment would provide anindication of the patient's absolute fracture risk. In this respect,T-scores and relative risk measurements are inadequate. For example, a70 year old patient with a T-score of −2 and relative risk of 4 has muchgreater absolute fracture risk than a 50 year old patient with the sameT-score and relative risk.

SUMMARY OF INVENTION

[0008] The present inventors have recognized that measurement of BMDproduced by densitometry equipment, cannot alone provide an indicationof absolute fracture risk. To the contrary, current studies show thatabsolute fracture risk is strongly dependent on factors that areindependent of BMD, in particular, age and gender. Other factors whichaffect absolute fracture risk include: whether the patient is a smoker,the amount of exercise the patient gets, how much the patient is onhis/her feet, the patient's history of fractures, the patient's familyhistory of fractures, and the long axis length of the patient's hip (hipaxis length). It is likely that additional risk factors will bediscovered.

[0009] The present invention therefore provides a bone densitometer thataccepts additional patient data to produce an output measurement ofabsolute fracture risk. The physician and patient are presented withthis absolute fracture risk contemporaneously with the measurement ofBMD, reducing patient confusion about T-scores and relative risk, andeliminating the need for cumbersome additional calculations by thephysician.

BRIEF DESCRIPTION OF DRAWINGS

[0010]FIG. 1 is a simplified perspective view of an x-ray bonedensitometer providing for lateral scanning or anterior/posteriorscanning of a patient with an x-ray fan beam under the control of acomputer;

[0011]FIG. 2 is a bone image of the femur such as may be acquired fromthe apparatus of FIG. 1 showing measurement of patient hip axis lengthand placement of a region of interest on the neck of the femur;

[0012]FIG. 3 is a graph plotting as vertical bars average bone densityin the region of interest of FIG. 2, average bone density of a standardindividual for the same region of interest, and standard deviation ofmeasurement of the standard individual used in the calculation ofT-score;

[0013]FIG. 4 is a flow chart showing steps performed by a programexecuted by the computer of FIG. 1 to provide an output measure ofabsolute fracture risk;

[0014]FIG. 5 shows an example of a graphic output of absolute fracturerisk;

[0015]FIG. 6 is an example of a tabular output of absolute fracturerisk;

[0016]FIG. 7 is a figure similar to that of FIG. 2 showing use of theinvention on lumbar vertebrae and a positioning of a region of interestupon one vertebra; and

[0017]FIG. 8 is a simplified perspective view of an ultrasound bonedensitometer measuring the os calcis of the heel.

DETAILED DESCRIPTION

[0018] Referring now to FIG. 1, an x-ray bone densitometer 10 mayinclude a patient table 12 providing a horizontal surface for supportinga patient in supine position along the longitudinal axis 16.

[0019] A C-arm 18 may have a lower end positioned beneath the patienttable 12 to support an x-ray source 20 and, an upper end positionedabove the patient table to support an opposed x-ray detector 22. Thex-ray source 20 produces a fan beam 24 whose plane is parallel to thelongitudinal axis 16, and which, in the preferred embodiment, providestwo x-ray energies. The x-ray detector 22 may be a multi-element CZTdetector discriminating between the energies of x-rays. Other methods ofdual energy measurement, including those providing for rotating filterwheels or variations in x-ray tube voltage, may also be used, as maymonoenergetic techniques of measuring bone density, as will beunderstood in the art.

[0020] The x-ray source 20 and x-ray detector 22 may be moved in araster pattern 25 so as to trace a series of transverse scans 33 of thepatient during which dual energy x-ray data is collected by the x-raydetector 22. The raster pattern 25 is adjusted so that there is a slightoverlap between successive scan lines of the fan beam 24 to provide someheight data. During this scanning, the x-ray source 20, the x-raydetector 22, and the translation controller 19 communicate with and areunder the control of computer 26 which may include dedicated circuitryand/or one or more processors. The operation of the computer 26 is underthe direction of a stored program portion of which will be described indetail below.

[0021] The computer 26 communicates with a terminal 28 including adisplay 30 and a keyboard 31 and a cursor control device such as a mouse35 allowing for operator input of patient data, as will be described,and the output of text and/or images to the operator providing theresults of the scan.

[0022] During operation of the bone densitometer 10 to acquire bonemineral density (BMD) data, the computer 26 will communicate with thetranslation controller 19 to scan a region of interest (37 or 38) of thepatient 14 in one or more transverse scans 33. Along each scan, datawill be collected associated with different rays of the fan beam 24measuring attenuation at two distinct x-ray energy levels. The twomeasurements of attenuation for different x-ray energies may be combinedto produce a bone image substantially independent of attenuation by softtissue.

[0023] Referring now to FIG. 4, in a first step of a stored programexecuted by computer 26 of FIG. 1, indicated by block 40, patientinformation is entered into the computer 26. The information may beentered through the keyboard 31 or through a menu structure and mouse 35or by transfer of the data from another patient record system.

[0024] These data will generally include quantitative informationrelated to risk of fracture other than BMD and will typically includethe age and gender of the patient. The present invention alsocontemplates, however, the use of additional patient informationincluding, for example, the patient's smoking habits (smoker ornon-smoker), the amount of exercise the patient performs, the patient'smobility (for example, how much time the patient is on his or her feetduring the day or whether the patient can get out of a chair withoutusing his or her arms, or similar measures), the patient's history andpatient's family history of fragility fractures, whether there are crushfractures of patient vertebra, and patient hip axis length. These lattertwo quantities may be determined alternatively by the scanning processdescribed below and input without physician intervention.

[0025] After the non-BMD patient information is input at succeedingprocess block 42, a scan is conducted of the patient to produce a boneimage. Typically, as shown in FIG. 1, the scan will be either of aregion of interest 38 about the hip of the patient or a region ofinterest 37 in the area of the lower or lumbar spine region. For thehip, the region of interest 38 may be the femoral neck, trochanter,femoral shaft, Ward”s region, or the total femur.

[0026] Referring now to FIG. 2, for a bone image 32 of the patient'sfemur 34, a determination of patient hip axis length 36 may be derivedand used as one of the non-BMD inputs described above. Such measurementmay be made by the placement of cursors on the image on display 30 bythe operator using the cursor control device 35 or through automatic orsemi-automatic procedures known in the art in which fiducial points areidentified on the bone using a template structure or the like and thedistance mathematically calculated.

[0027] A similar mechanism may be used to place a measurement region 39on the neck of the femur 34 defining an area in which the BMDmeasurements will be combined to yield an average bone density over themeasurement region 39.

[0028] At process block 44, the average bone density over themeasurement region 39 is converted to a standard BMD value according totechniques well known in the art to compensate for differences betweendensitometers 10 from different manufacturers caused by differentdefinitions of the measurement regions 39 and different measurementtechniques.

[0029] Next, at process block 46, a T-score is calculated from thestandard BMD value. Referring to FIG. 3, such T-scores are well known inthe art and compare the average bone density 48 found within themeasurement region 39, as corrected by process block 44, to an averagebone density 50 of a standard individual. By convention, the standardindividual is a statistical combination of individuals of average agethirty and the same gender as the patient. A standard deviation 52 forthe standard individual may be determined from measurements of theindividuals from whom the standard is prepared. The T-score is then thedifference between average bone density 48 (of the patient) and averagebone density 50 (of the standard individual) indicated by distance 54divided by the standard deviation 52.

[0030] After computation of the T-score, which may also be output to theoperator at process block 56, the present invention computes an absolutefracture risk. The computation of absolute fracture risk may be risk ofhip fracture or the risk of any fracture and uses the average bonedensity 48 (per FIG. 3) and the patient information (per process block40) of age and gender.

[0031] The process of determining absolute fracture risk uses severalpublic data sets. The first data set provides average BMD (or itsequivalent) for a normative set of individuals classified by age. Suchdata is, for example, available from the government sponsored studies,such as the National Health and Nutrition Examination Survey (NHANES)(see www.cdc.gov/nchs/nhanes). This first data set is combined with anempirically determined second data set providing fracture rate forindividuals of these same age classifications. The result is an averageabsolute fracture rate for each age group.

[0032] The third data set provides relative risk of fracture for givendecreases in BMD for each of the age classifications. This relative riskis made into an absolute risk for the patient by adjusting the averageabsolute fracture rate for the age group of the patient by the relativerisk caused by the difference between the patient's BMD and the averageBMD for the patient's age group.

[0033] Thus, the absolute fracture risk can be calculated for anindividual patient, by determining the deviation of the individualpatient's BMD value from the BMD normal to the patient's age group andapplying the relative risk for that age group to the absolute fracturerisk of that age group to determine the absolute fracture risk for theindividual patient.

[0034] These relationships may be reduced to a set of curves held intabular form or to explicit equations according to techniques well knownin the art. These data may be smoothed by interpolation to obtain acontinuous function. In addition, the absolute fracture estimate can berefined for different countries based on information regarding therelative fracture rates in each country. As additional research isprepared, additional factors may be incorporated into these equations orcurves.

[0035] The underlying data and this methodology is described generallyin the following public papers: “Meta-Analysis Of How Well Measures OfBone Mineral Density Predict Occurrence Of Osteoporotic Fractures”,Marshall et al., Br. Med. J. 312:1254-1259 (1996); “Risk of Hip FractureDerived From Relative Risks: An Analysis Supplied to the Population ofSweden”, Kanis et al., Osteoporosis Int., 11:120-127 (2000);“Prospective: The Diagnosis of Osteoporosis”, Kanis et al., J. BoneMiner. Res., Vol. 9, No. 8:1137-1141(1994); “Ten Year Probabilities ofOsteoporotic Fractures According to BMD and Diagnostic Thresholds”,Kanis et al., J. Bone Miner. Res. Vol. 16 (Suppl 1):S194 (2001), Kaniset al.; “Ten Year Probabilities of Osteoporotic Fractures According toBMD and Diagnostic Thresholds”, De Laet et al., J. Bone Miner. Res. Vol.13, No. 10:1587-1593 (2002); “Identification and Fracture Outcomes ofUndiagnosed Low Bone Mineral Density in Post-Menopausal Women: ResultsFrom the National Osteoporosis Risk Assessment”, Siris et al., JAMA Vol.286 No. 22:2815-2822 (2001).

[0036] These results may be modified by a number of multipliers for riskknown in relationships with the other patient input variables. Forexample, each 6 mm increase in hip axis length (compared to height- andweight-adjusted average) increases risk by a factor of 1.6. A smoker hasan increased risk for fracture of 1.3 compared to non-smokers. Subjectswith low mobility (less than 4 hours of time on their feet per day) orwho are unable to raise from a chair without the use of their arms havean increased fracture risk of 2.0 in each case. In the presence of theseor other additional risk factors, absolute risk estimates can be furtherrefined by multiplying the risk determined from the BMD and age modelsby the appropriate relative risk coefficients reported in the scientificliterature.

[0037] At succeeding process block 58, the results of the absolute riskcalculation may be output. Referring to FIG. 5, in a graphical output,the T-score may form a vertical axis of a graph 59 with patient age asthe horizontal axis. The patient's T-score, as computed at process block46, is plotted on the graph as plot point 60 for the patient's inputage.

[0038] The background of the graph includes three separate bands 62, 64and 66 representing low, medium, and high absolute fracture risks,respectively. Generally, band 62 indicates low absolute fracture risk(colored green in this example), band 64, positioned below band 62,indicates medium absolute fracture risk (colored yellow in thisexample), and band 66, positioned below band 62, and indicates a highabsolute fracture risk, (colored red in this example).

[0039] The interface between band 62 and 64 indicates a 10% fracturerisk during the next ten years and the interface between bands 64 and 66indicates a 20% fracture risk during the next ten years. This selectionof thresholds of 10% and 20% conforms to thresholds used for thetreatment of high blood cholesterol in adults as determined by theNational Cholesterol Education Project (NCEP) and thus is familiar tophysicians. The strength of the relationship between fractures and bonedensity, however, is stronger than the analogous relationship betweenlipid levels and coronary heart disease.

[0040] The alignment of the three bands 62, 64, and 66 with T-score alsoprovides a classification of the patient that conforms generally to adivision prepared by the World Health Organization for the assessment ofosteoporosis in populations. Thus, at age 65, when the fracture riskincreases significantly, a ten year risk for any fracture of 20% occursat the femoral T-score of −2.5 matching the WHO category of osteoporosisbased on a BMD 2.5 or more standard deviations below a young adult BMD.Likewise, a ten year risk for any fracture of 10% at age 65 equates to afemoral neck T-score of −1 matching the WHO category of low bone mass(osteopenia) based on a BMD between 1 and 2.5 standard deviations belowa young adult BMD. Thus, the graphic representation provides consistencywith the well known categorizations of normal, osteopenia, andosteoporosis defined by the WHO at an age where fracture risk incidencebegins to increase dramatically (65 years). However, it is important torecognize that the WHO criteria were defined for populations rather thanindividuals.

[0041] Note that the bands generally rise with age reflecting the factthat for a given BMD value, risk increases as the patient becomes older.This must be compared to standard BMD and T-score values which remainconstant for a given bone mass with the aging process. The particularshape of the bands 62, 64 and 66 will depend on the patient data used.If additional risk factors are included, these bands may be shifted bythose risk factors.

[0042] Referring to FIG. 6, the information may also be provided intabular form with a first row of a table 70 providing in a first column,the patient's name and age, in the second column, the ten year risk forhip fracture, and in a third column, the ten year risk for any fracture.In a second row, the first column indicates a reference populationhaving the same age as that of the patient. In a second column of thesecond row, the ten year risk for hip fracture for that population isprovided, and in a third column, the ten year risk for any fracture forthat population is provided.

[0043] Referring now to FIG. 7, the densitometer 10 of FIG. 1 also maybe employed for the measurement of BMD from a region of interest 63located in a trabecular region of a lumbar vertebra 65. Standardmorphometric techniques may be used to detect crushed vertebra 65′ suchas indicate fragility fractures which may also be used in thecalculation of absolute risk as one of the patient input factorsdescribed above. Presence of a fragility fracture represents a strongrisk factor for future osteoporotic fractures, which can be incorporatedinto the absolute risk model.

[0044] Referring to FIG. 8, the present invention is also applicable toultrasonic densitometers 73 in which an ultrasonic transducer 71provides an ultrasonic signal passing through the os calcis 72 of apatient's foot 74. The ultrasonic signal is received by a detector 76and processed by computer 80 to determine speed of sound (SOS) orbroadband ultrasonic attenuation (BUA) or combinations of the two as arewell known in the art. Patient data may be entered through an associatedkeyboard 82 and output data provided on output display 84 according towell-known techniques in the art.

[0045] Thus, the present invention, by accepting additional patientdata, provides an accurate measurement of absolute risk, rather thanrelative risk, as is desired by patients and physicians. Absolute riskassessment is a more accurate representation of risk than T-scores orrelative risk measures that can either overstate, in the case of youngerindividuals, or understate, in the case of the elderly, the truefracture risk.

1 A computerized densitometer comprising: an energy source and detectoropposable about a patient to produce signals indicating energymodification by bone of the patient; means for receiving patientinformation other than energy modification information; a computerreceiving the signals and patient information and executing a storedprogram to: (a) control the energy source and detector to acquire energymodification signals for a plurality of points over a scan area; (b)calculate, for the plurality of points, bone density; (c) determine fromthe bone density and patient information, an absolute risk of bonefracture in the patient over a predetermined period of the future; and(d) output the absolute risk of bone fracture. 2 The computerizeddensitometer of claim 1 wherein the energy source is a source ofultrasound and the computerized densitometer is an ultrasonicdensitometer. 3 The computerized densitometer of claim 1 wherein thescan area is the os calcis. 4 The computerized densitometer of claim 1wherein the energy source is an x-ray source and the computerizeddensitometer is an x-ray densitometer. 5 The computerized densitometerof claim 1 wherein the scan area a portion of the femur, selected from agroup consisting of the femoral neck, trochanter, femoral shaft, Ward”sregion, and the total femur. 6 The computerized densitometer of claim 1wherein the scan area is at least one vertebra. 7 The computerizeddensitometer of claim 1 wherein the x-ray source provides dual energiesof x-rays and the detector operates to distinguish between attenuationat each of the dual energies. 8 The computerized densitometer of claim 1wherein the patient information is selected from the group consistingof: age, gender, habit of smoking; habit of exercise, patient mobility;patient history of fragility fractures, and patient hip axis length. 9The computerized densitometer of claim 1 wherein the computerizeddensitometer further includes a graphics output device and wherein andthe output of absolute risk is a point plotted on a graph having avertical axis related to bone mineral density and a horizontal axis ofpatient age, the graph further having delineated bands defining regionsof absolute risk of fracture. 10 The computerized densitometer of claim9 wherein the delineated bands indicate lines of 10% and 20% absoluterisk of fracture. 11 The computerized densitometer of claim 10 whereinthe area of the graph in a region of less than 10% absolute risk offracture is green, the area of the graph in a region between 10% and 20%absolute risk of fracture is yellow and the area of the graph in aregion of greater than 20% absolute risk of fracture is red. 12 Thecomputerized densitometer of claim 9 wherein the vertical axis of thegraph is T-score. 13 The computerized densitometer of claim 10 whereinthe vertical axis of the graph is T-score and wherein the line of 10%absolute risk of any fracture crosses age 56 at a T-score of −1.0 andthe line of 20% absolute risk of any fracture crosses age 65 at aT-score of −2.5%. 14 The computerized densitometer of claim 1 whereinthe output of absolute risk is a risk of hip fracture for the patient.15 The computerized densitometer of claim 14 wherein the predeterminedperiod of the future is ten years. 16 The computerized densitometer ofclaim 15 wherein the output further includes average absolute risk ofhip fracture for a period of the future of ten years for a population ofthe same age and gender as the patient. 17 The computerized densitometerof claim 1 wherein the output of absolute risk is a risk of any bonefracture for the patient. 18 The computerized densitometer of claim 17wherein the predetermined period of the future is ten years. 19 Thecomputerized densitometer of claim 18 wherein the output furtherincludes average absolute risk of any bone fracture for a period of thefuture of ten years for a population of a same age and gender as thepatient. 20 The computerized densitometer of claim 1 wherein the scanregion is femur and wherein the computer further executes the storedprogram to measure a patient hip axis length and wherein the measuredpatient hip axis length is used as the patient information.